This research seeks to understand the molecular basis of erythrocyte membrane elasticity and failure. Micromechanical experiments will be performed on individual cells to obtain measurements of intrinsic membrane mechanical properties and to determine the changes in these properties because of specific alterations in the molecular structure of the membrane skeleton and changes in the physical environment within the cell. Advantage will be taken of the membrane skeletal abnormalities which occur in hereditary disorders such as hereditary spherocytosis, hereditary alliptocytosis, and hereditary poikilocytosis. The specific molecular alteration in the membranes of several individuals having this disorder has been identified. Measurement of altered mechanical properties of those membranes will enable us to draw specific conclusions about the relationship between molecular structure and mechanical function and increase our understanding of how these molecular changes affect the survival of these cells in the circulation. The particular membrane properties of interest include the surface elastic shear modulus, yield shear resultant, viscoelastic and plastic viscosities, coefficient of material relaxation and the area compressibility modulus. These properties will be measured using both novel and established techniques including micropipette aspiration and membrane tether formation. In order to broaden our understanding of cellular structures beyond the skeleton of mammalian erythrocyte membranes we will perform mechanical measurements on nucleated erythrocytes and marginal bands isolated from those cells to assess the contribution of the marginal bands to the cellular deformability. We will also perform measurements of reconstituted membrane systems to determine the contribution of the lipid bilayer and integral membrane proteins to membrane area compressibility ;and surface viscosity. This work is an important step toward understanding the structure - function relationships of the structural proteins of cellular skeletal systems.